This is a continuation of our long-term work on the physiology, biochemistry, and therapeutics of the carbonic anhydrase system, and the drugs that inhibit it. The following are the specific points that will be studied in the next year. 1) The mechanism of action of acetazolamide and other carbonic anhydrase inhibitors in glaucoma. This involves studies of the transport of ion from plasma to aqueous humor in primates. 2) The proper way to treat glaucoma with the carbonic anhydrase inhibitors will be reassessed, with particular emphasis on the dosage schedule of methazolamide, which appears safer than acetazolamide. 3) Physiology of formation of cerebrospinal fluid, with emphasis of ion transport during various metabolic changes and administration of certain drugs. An in vitro system is being developed for study of fundamental mechanism. 4) Renal studies of HCO3 excretion and the relations between the pCO2 of urine and distal tubular dysfunction such as seen in renal tubular acidosis of children. 5) Studies on the role of the human red cell enzyme called carbonic anhydrase B, but which does not have a function in CO2 transport. This may be related to thyroid and other diseases, but the primary goal is to discover the substrate for the enzyme. 6) Studies will be done to discover the mechanism by which acetazolamide is effective in the treatment of both hypo- and hyper- kalemic periodic paralysis. This involves tests on several families afflicted with the disease, in our Clinical Research Center. 7) Studies will be done with isotopically labelled water and carbonic anhydrase, to attempt to learn about the mechanism of catalysis.